scholarly journals Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha‐tocopherol, beta‐carotene cancer prevention (ATBC) study

2015 ◽  
Vol 137 (9) ◽  
pp. 2124-2132 ◽  
Author(s):  
Alison M. Mondul ◽  
Steven C. Moore ◽  
Stephanie J. Weinstein ◽  
Edward D. Karoly ◽  
Joshua N. Sampson ◽  
...  
2008 ◽  
Vol 123 (5) ◽  
pp. 1154-1159 ◽  
Author(s):  
Jiyoung Ahn ◽  
Roxana Moslehi ◽  
Stephanie J. Weinstein ◽  
Kirk Snyder ◽  
Jarmo Virtamo ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Alison M. Mondul ◽  
Steven C. Moore ◽  
Stephanie J. Weinstein ◽  
Anne M. Evans ◽  
Edward D. Karoly ◽  
...  

Background. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a randomized controlled cancer prevention trial, showed a 32% reduction in prostate cancer incidence in response to vitamin E supplementation. Two other trials were not confirmatory, however.Objective. We compared the change in serum metabolome of the ATBC Study participants randomized to receive vitamin E to those who were not by randomly selecting 50 men from each of the intervention groups (50 mg/day all-rac-α-tocopheryl acetate (ATA), 20 mg/dayβ-carotene, both, placebo).Methods. Metabolomic profiling was conducted on baseline and follow-up fasting serum (Metabolon, Inc.).Results. After correction for multiple comparisons, five metabolites were statistically significantly altered (βis the change in metabolite level expressed as number of standard deviations on the log scale):α-CEHC sulfate (β=1.51,p=1.45×10-38),α-CEHC glucuronide (β=1.41,p=1.02×10-31),α-tocopherol (β=0.97,p=2.22×10-13),γ-tocopherol (β=-0.90,p=1.76×10-11), andβ-tocopherol (β=-0.73,p=9.40×10-8). Glutarylcarnitine, beta-alanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation (βrange 0.40 to −0.36), but not statistically significantly.Conclusions. Comparison of the observed metabolite alterations resulting from ATA supplementation to those in other vitamin E trials of different populations, dosages, or formulations may shed light on the apparently discordant vitamin E-prostate cancer risk findings.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3873
Author(s):  
Liang Hu ◽  
Andrew Harper ◽  
Emily Heer ◽  
Jessica McNeil ◽  
Chao Cao ◽  
...  

We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer-free men aged 35–69 years enrolled in Alberta’s Tomorrow Project (ATP) from 2001–2007. In the 2008 survey, participants reported usual bed- and wake-times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0–<1 h (from 0 to anything smaller than 1), 1–<2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases (n = 250). Hazard ratios (HR) were estimated using Cox proportional hazards regressions, adjusting for a range of covariates. Median follow-up was 9.57 years, yielding 68,499 person-years. Baseline presence of social jetlag of 1–<2 h (HR = 1.52, 95% CI: 1.10 to 2.01), and 2+ hours (HR = 1.69, 95% CI: 1.15 to 2.46) were associated with increased prostate cancer risk vs. those reporting no social jetlag (p for trend = 0.004). These associations remained after adjusting for sleep duration (p for trend = 0.006). With respect to chronotype, the association between social jetlag and prostate cancer risk remained significant in men with early chronotypes (p for trend = 0.003) but attenuated to null in men with intermediate (p for trend = 0.150) or late chronotype (p for trend = 0.381). Our findings suggest that greater than one hour of habitual social jetlag is associated with an increased risk of prostate cancer. Longitudinal studies with repeated measures of social jetlag and large samples with sufficient advanced prostate cancer cases are needed to confirm these findings.


2015 ◽  
Vol 27 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Jeannette M. Schenk ◽  
Cathee Till ◽  
Ann W. Hsing ◽  
Frank Z. Stanczyk ◽  
Zhihong Gong ◽  
...  

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Trond Heir ◽  
Ragnhild Sørum Falk ◽  
Trude Eid Robsahm ◽  
Leiv Sandvik ◽  
Jan Erikssen ◽  
...  

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1810-1810
Author(s):  
Jiaqi Huang ◽  
Stephanie Weinstein ◽  
Wendy Mack ◽  
Howard Hodis ◽  
Demetrius Albanes

Abstract Objectives Vitamin E is an essential micronutrient and critical human antioxidant that has been tested for cancer and cardiovascular preventative effects for decades with conflicting results. For example, prostate cancer incidence was reduced by a low-dose vitamin E supplement in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, but the findings were not replicated by high-dose vitamin E trials such as the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The present investigation examined the serum metabolomic responses to low- and high-dose vitamin E supplementation in order to gain biological insight into the divergent trial outcomes. Methods We examined baseline and on-study serum samples for 154 men randomly assigned to receive 400 IU vitamin E (as alpha-tocopheryl acetate; ATA) or placebo daily in the Vitamin E Atherosclerosis Prevention Study (VEAPS), and 100 men administered 50 IU ATA or placebo daily in the ATBC Study. Over 970 known metabolites were identified using an ultrahigh-performance LC-MS/MS platform. Linear regression models estimated the change in serum metabolites of men supplemented with vitamin E to those assigned to placebo in VEAPS compared with ATBC. Results Serum alpha-carboxyethyl hydrochroman (CEHC) sulfate, alpha-tocopherol, and beta-/gamma-tocopherol were significantly altered by supplementation with ATA in both the VEAPS and ATBC trials (all P-values ≤ 5.1 × 10−5, the Bonferroni multiple-comparisons corrected statistical threshold). Serum C22 lactone sulfate was also significantly decreased in response to the high-dose vitamin E supplement in VEAPS (β = −0.70, P-value = 8.1 × 10−6), but not altered in the low-dose ATBC trial (β = −0.17, P-value = 0.4). Additionally, changes in several androgenic steroid metabolites were strongly related to the vitamin E supplement-associated change in C22 lactone sulfate only in the high-dose VEAPS trial. Conclusions We found evidence of a dose-dependent vitamin E supplementation effect on a novel C22 lactone sulfate compound as well as several androgenic steroids that may have relevance to previous controlled trial findings for prostate cancer. Funding Sources This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, U.S. Public Health Service, Department of Health and Human Services.


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